Cirrhosis TIPS for the decompensated cirrhotic & acute on chronic liver failure from expert hepatologist and keto-practitioner Scott Matherly MD, @liverprof and chief hepatologist at @KashlakHospital. We walk through acute management of variceal bleeds, when to suspect SBP in decompensated cirrhosis (all the time, it turns out), how much fluid to remove in paracentesis, and some definitions about what decompensated cirrhosis and acute on chronic liver failure really mean.
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Written and produced by: Nora Taranto MS4, Matthew Watto MD
Pretest by: Cyrus Askin MD
Hosts: Matthew Watto MD, Paul Williams MD,
Images and infographics: Hannah Abrams MS3
Edited by: Matthew Watto MD
Guest: Scott Matherly MD
Remember your ABCs. Patients with acute hepatic encephalopathy may need intubation (airway protection). When a patient walks in with a suspected variceal bleed, place 2 large bore IVs, and start fluids (blood and crystalloid). Albumin is not a resuscitation fluid!
Give octreotide and prophylactic antibiotics IMMEDIATELY for variceal bleeding. Perform an endoscopy for banding within 12 hours.
After a variceal bleed, start a nonselective Beta Blocker (e.g. propranolol or nadolol). As long as the systolic blood pressure is >90, beta blockers are recommended. You may also consider a TIPS procedure in certain patients to reduce portal pressures and risk of rebleeding.
In a cirrhotic patient who is not bleeding, expert opinion is to give DVT prophylaxis with enoxaparin or heparin unless platelets are lower than 50. The INR is not useful in these patients to predict their coagulopathic status because it does not account for both the pro- and anti- coagulant losses that occur in chronic liver failure.
DO NOT get an ammonia level on patients with a history of cirrhosis.
Always suspect infection [specifically Spontaneous Bacterial Peritonitis (SBP)] in a cirrhotic patient coming in with acute decompensation. SBP has protean manifestations. Abdominal pain and fevers are not always present.
Suspect Spontaneous Bacterial Peritonitis? Perform a small volume paracentesis immediately at bedside. Send fluid studies including cell count and differential, and culture. Always culture the fluid in a blood culture vial at bedside to increase yield (Dr Matherly’s expert opinion) —Runyon J Clin Microbiol 1990. Start antibiotics and fluids immediately.
Hepatic Encephalopathy workup: Look for an acute precipitant. Rule out some of the common causes: infection, bleeding, overmedication (benzodiazepines, narcotics) or undermedication (not taking lactulose), hypokalemia or other electrolyte abnormalities, volume depletion, or increased shunting because of a thrombosis or malignancy.
The prospect of managing a patient who walks in with the acute complications of cirrhosis–whether it’s a variceal bleed, spontaneous bacterial peritonitis, hepatic encephalopathy, hepatorenal syndrome, or something else–is terrifying to most of us non-hepatologists. These patients are often on the brink of rapid decompensation (if not already past it), and their risk of dying while admitted is scarily high.
Diagnosed with cirrhosis based on history, physical exam, and lab abnormalities but without history of ascites, encephalopathy, or variceal bleeding. Prognosis is good in the long term (survival measured in decades). Compensated cirrhosis can be broken down into those with and without varices (D’Amico et al, 2006), or with or without portal hypertension.
Cirrhosis with ascites, hepatic encephalopathy, or variceal bleeding. Prognosis becomes poorer once patients experience one of these, and these patients benefit from evaluation for transplant. (n.b. Patients can move fluidly between these categories. An alcoholic patient with decompensated cirrhosis who then stops drinking, or a patient with Hepatitis C who starts the anti-viral therapy, may experience dramatic improvements in a short amount of time. These patients might be considered compensated after several years.
Cirrhosis with recurrent variceal bleeds, refractory ascites, hepatorenal syndrome, recurrent hepatic encephalopathy, or continuous jaundice. Much poorer prognosis (survival measured in months or less). These patients require immediate consideration for transplant.
A syndrome of acute decompensation of patient with prior underlying liver disease (cirrhosis or otherwise) characterized by the development of liver failure (jaundice, elongated INR) and one or more extra-hepatic organ failures (renal failure, hypotension, encephalopathy/CNS failure). Mortality is as high as 50-70% during the acute admission.
These scoring mechanisms prognosticate survival over a longer time scale–months to years–rather than days to weeks. Therefore, they are not particularly useful for prognosticating acute complications in the cirrhotic patient. The Child-Pugh Score roughly aligns with compensated (Child A) and decompensated (Child C), and so can be used to broadly summarize functional status in the non-acute setting. The MELD score has more recently become the main prognostic tool, but prognosticates mortality over a three-month course, not in the short term. The best, and only, acute prognosticating score tool is the CLIF score, which is a modified Sequential Organ Failure Assessment (SOFA) tool and is mostly used in the ICU to assess the likelihood of improving clinical status with continued intervention.
First and foremost, lay eyes on the patient. Do your ABCs. Is the patient able to protect his or her airway? In liver patients, aspiration can lead to very quick decompensation and death. So if the patient is vomiting or obtunded, think about intubation and ICU admission. AND, vitals are vital!; the patient could be bleeding profusely/quickly from varices; or could be in septic shock.
On further history, ask family members about dark stools, blood thinners, NSAIDs, medications that would alter sensorium (benzodiazepines, narcotics), alcohol use, and any recent history of falling.
Look for ascites, and listen for pulmonary edema. (This wouldn’t be the time to look for asterixis since the patient is altered, and therefore, presumed encephalopathic).
On labs, particularly worrisome findings would include a low sodium (which suggests Hepatorenal syndrome), elevated BUN and low Hemoglobin (which would indicate upper GI bleed).
It’s related to shunting, plain and simple (or not so simple; how this happens is pretty complex). Hepatic encephalopathy can occur in patients with cirrhosis and without (though cirrhosis increases the risk). But first, look for the cause or precipitant.
Infection, Bleeding (Variceal or otherwise), Over-Medication (benzodiazepines, narcotics, GABA-ergic medications), Under-Medication with Lactulose, Hypokalemia, Volume depletion, Increased shunting due to thrombosis or malignancy (get a liver doppler) . You need to rule these out!
The mainstay of treatment for HE, when those causes have been ruled out, is Lactulose (until very frequent bowel movements). Or, use lactulose plus PEG. Lactulose can be given orally. BUT, Lactulose PR (enema) is the way to go if the patient is obtunded. Rifaxamin is a very effective second line. Use is limited by cost. It’s expen$ive! For more info about management of HE, check out Elliott Tapper, master hepatologist’s tweetorial: @ebtapper’s amazing tweetorial on Hepatic Encephalopathy.
Immediately upon seeing a hypotensive patient with cirrhosis and a history of varices, you should place two large bore IVs and start fluid resuscitation for hypotension. You can resuscitate with crystalloid and blood (25% albumin won’t cut it). Hemoglobin goals for cirrhotics should be 7-9 gm/dL (Villaneuva et al 2013). Actually, transfusing to higher thresholds can increase the risk of bleeding. Dr Matherly recommends getting the patient to endoscopy within 12 hours for banding. Also, start octreotide (or Terlipressin, if outside the United States) as soon as possible. Give octreotide as a bolus. Then, follow with continuous infusion for 3-5 days.
In patients with variceal bleeds, give antibiotics (either a third-generation cephalosporin or higher if very sick) for five days. In these patients, especially those with ascites, you must rule out and treat infection. Dr Matherly cautions, the clinical picture may be innocuous until a patient is fully septic (Note: these patients may be hypotensive at baseline). Get blood and urine cultures, a chest x-ray, and perform diagnostic paracentesis on all of these patients! Any cirrhotic admitted to the hospital, for whatever reason, who has ascites has Spontaneous Bacterial Peritonitis (SBP) until proven otherwise. –Dr. Matherly’s expert opinion
Dr Matherly revealed that large, scary ulcers develop in the lower esophagus after banding of esophageal varices. He notes that proton-pump inhibitors may help prevent bleeding from post-banding ulcers –Kang SH Medicine (Baltimore) 2016. PMC4779029. PPIs DO NOT have efficacy for variceal bleeding since it’s a pressure phenomenon.
Hemoccult tests (if the patient came in with melena or throwing up blood, you can assume this is in fact a GI bleed) and Ammonia Levels (neither indicated nor useful in a decompensated cirrhotic).
Don’t measure Ammonia levels in cirrhotics. Drawing ammonia levels on cirrhotics leads to harm of patients; they end up being told to take huge amounts of Lactulose just because of the elevated ammonia level rather than because they are actually confused and encephalopathic (which is a clinical diagnosis), and which would warrant taking Lactulose.
Urea cycle disorders in kids; someone without cirrhosis who is altered without known cause; acute liver failure due to acetaminophen overdose (in which ammonia level can help prognosticate).
Propranolol and nadolol are effective at reducing portal pressure and reducing risk of secondary variceal bleeds. Do NOT start these if the systolic blood pressure is <90 mmHg, or potentially in patients with refractory ascites. Consider a TIPS procedure if the patient’s pressure drops too low on beta blockers.
Transjugular Intra-hepatic Portosystemic Shunt (TIPS), placed by Interventional Radiology to artificially connect the portal vein to hepatic vein. This procedure creates a shunt so that blood can pass from the portal vein to the IVC without going through the fibrotic, high-pressure liver system. TIPS immediately decreases portal pressures to sub-bleeding levels (not necessarily to normal).
High hepatic venous pressure gradients, very high portal HTN greater than 20 mmHg, or a Childs B or C cirrhotic who is still bleeding after banding.
If the liver is too sick, this procedure can cause acute liver failure by shunting blood away from it. Moreover, if the patient has pulmonary hypertension, the TIPS can cause death from increased preload. Furthermore, 30-40% people will develop encephalopathy, which is largely a shunting phenomenon (Fonio et al. 2017). Consult your friendly neighborhood hepatologist to provide tips on TIPS if you’re unsure of where your patient lies in this algorithm.
Bleeding tends to be a pressure-based phenomenon. It’s NOT a true coagulopathy. In general, bleeding happens more in cirrhotics. At the same time, we think (the data is a little controversial) that cirrhotics clot at higher rates than average. They frequently get portal venous thrombosis, and DVTs. These clots can be devastating in an already-sick cirrhotic patient.
A 2012 RCT found no difference in bleeding between cirrhotic patients put on enoxaparin versus placebo, but fewer episodes of portal venous thrombosis, fewer episodes of decompensation, and increased survival in the enoxaparin group than in the placebo group (Villa et al, 2012)
Kashlak Pearl: We should be prophylaxing patients with enoxaparin or heparin for DVT prophylaxis unless there is some reason not to (e.g. if platelets are under 50-60K). –Dr. Matherly’s expert opinion about DVT prophylaxis.
The liver makes all clotting factors except VIII (made by endothelial cells). So, all procoagulant and most anti-coagulant factors tend to be low in chronic liver disease. This means that the balance is quite tenuous. It can tip either way pretty quickly. But, the INR (which can tell us about liver function) cannot tell us about coagulopathy because it measures only the clotting factor deficiencies, NOT the anticoagulant deficiencies (Thrombomodulin is not in the assay). It’s just not useful.
Kashlak Pearl: The INR tells you about the bleedy, but NOT the anti-bleedy side of the equation. –Dr Matherly’s eloquent description ; )
Moreover, fixing the INR to normal range does not actually improve outcomes, (whether with factor VII if that’s the main deficiency or FFP). When you give just pro-coagulant factors to improve the INR to a level you are comfortable with, you ignore the anticoagulant deficiencies that are present in liver disease and therefore push the patient towards a pro-clotting picture. These patients may very well clot off their portal veins or mesenteric vasculature. Dr Matherly notes that FFP, Factor VII, and Vitamin K (unless you suspect the patient is vitamin K deficient for some reason) are not helpful.
Hepatologists love them. Nephrologists don’t so much (taking lots of fluid off = sad kidneys). If a patient has ascites and you want to rule out infection, do a diagnostic, lower-volume paracentesis (2-3 Liters). Then, later on, you can do a therapeutic large-volume paracentesis as needed. The hepatologist’s rule, in patients without signs of sepsis: tap until dry, and then give albumin. Other, good ways to deal with ascites: Low Sodium Diet, and Diuretics.
Send SAAG labs (serum ascites – serum albumin gradient).
Kashlak Pearl: Dr Matherly notes, “The liver sinusoid, which is the liver’s capillary, is built, is evolutionarily created to keep albumin in the blood vessel.” In cirrhosis, the liver becomes scarred and the sinusoids lose their fenestrations. After this occurs, albumin and small proteins are even less likely to make it out of the sinusoids. Thus, the ascitic fluid becomes increasingly protein poor.
Cirrhosis causes a High SAAG, above 1.1, ascites. A high SAAG tells you that the fluid is coming from the liver sinusoid due to a high pressure and volume gradient. Cirrhotic ascites is protein-poor and albumin-poor with a high SAAG. The scarred down liver sinusoids don’t allow the escape of albumin (large molecule). In non-cirrhotic ascites (e.g. cardiac ascites), the fluid has a high SAAG and high protein (e.g. in right sided heart failure, budd chiari, pulmonary hypertension).
Ascites with low SAAG, under 1.1, suggests albumin levels in the serum are nearly equal to the ascitic fluid. This denotes ascites from an extra-hepatic source. Causes include: infections, peritoneal carcinomatosis, malignancy, renal failure, and pancreatitis.
The ever-feared SBP kills cirrhotics. And, it can be a silent infection (without fever, abdominal pain, or other symptoms). The first presentation may be encephalopathy, or a variceal bleed.
Bacteria translocate out of the gut, into the blood, and seed the peritoneal space. Ascitic fluid can’t rid itself of translocated bacteria because it is protein-poor (and therefore IgG- and complement-poor) and cannot fight off infection.
If you are concerned about SBP (ie if a cirrhotic patient comes in with ascites and any acute changes), do a diagnostic paracentesis (2-3L) right off the bat. Send the fluid for SAAG, protein, cell count, and fluid culture. Send blood cultures as well. Dr Matherly recommends inoculating a blood culture vial from the ascitic fluid, and sending it for fluid culture. He cites an increase in yield by as much as 30% (Runyon et al. 1990).
A fluid cell count of more than 250 neutrophils (PMNs) without another cause (like a perforated viscous or another intra-abdominal infection) is diagnostic of SBP. The fluid will often be cloudy.
Start antibiotics as soon as possible. Typically treat with five days IV Ceftriaxone (or even broader spectrum if suspicious for MDRO). You should see a dramatic improvement in the patient within those 5 days. Repeat the paracentesis after antibiotic treatment if you are concerned about incomplete resolution. Patients will need lifelong secondary SBP prophylaxis (usually with oral fluoroquinolones).
Replace the albumin you have removed with the paracentesis. The SORT trial (Sort et al. 1999) found a dramatic reduction in mortality in patients with SBP who were given albumin versus those who were not given albumin replacement. This replacement albumin should keep blood more in the vasculature instead of causing compartmental shifting with fluid removal after paracentesis.
Kashlak Pearl: A general rule for albumin replacement in paracentesis = Give 50 gm Albumin (typically in 25% Albumin solution) for the first 5 liters removed. Then, given another 25 gm for the next 5 liters (total 10 liters). Dr Matherly does not exceed a total 100 gm albumin per day.
After a diagnosis of SBP, patients must be on secondary prophylaxis for life (Ciprofloxacin 250-500 mg per day).
Cirrhosis leads to disordered Cardiovascular blood flow as blood pools in the dilated mesenteric vessels (due to nitric oxide). This causes low systemic blood volume and arterial blood pressure. The kidney and brain become unhappy and release vasoactive substances to increase systemic blood pressure. But, blood pooling in the gut prevents an effective increase in blood pressure. A vicious cycle of worsening vasoconstriction in the periphery, renin and angiotensin activation, vasopressin release, and overall adrenergic outflow develops. These hormones lead to progressive renal vasoconstriction and the kidneys end up “squeezing themselves off.”
Development of acute renal failure in a matter of days. These patients require transplant for survival. Mortality is measured in days to weeks.
A slower, more insidious process with less extreme hepatorenal physiology. Patients may not have overt kidney failure (or elevated creatinine). Mortality is measured in months.
Development of Hyponatremia when placed on diuretics. Creatinine is not as useful. The MELD-Na score takes account of the dire prognosis associated with the development of hyponatremia in cirrhotics (it portends HRS in short order).
Listeners will feel confident in diagnosing and managing the acute complications of cirrhosis including spontaneous bacterial peritonitis, variceal bleeding, hepatic encephalopathy, and coagulopathy.
After listening to this episode listeners will…
Dr. Matherly reports no relevant financial disclosures. The Curbsiders were sponsored by the American College of Physicians for this episode.
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